Chemicals affect living organisms in both positive and negative ways. A new drug can save lives, or an environmental contaminant can create health problems. Sometimes, the same chemical can have both positive and negative effects, such as a drug that cures a disease but also has side effects. Multiple chemicals can interact to produce unexpected effects, for example when some medications taken in combination lead to side effects. For example, terfenadine (SELDANE®) was removed from the market in 1998 because its interaction with other drugs resulted in fatal heart arrhythmias. One study in the U.S. attributed as many as 100,000 deaths per year in the U.S. to such adverse drug reactions (ADR), making it between the 4th and 6th leading cause of death.
Chemicals can have different effects on different organisms, for example, potential drugs that work in animal studies, but later fail in human trials. Chemical effects also differ between individuals. Many medications only help a percentage of patients because patients respond to drugs in different ways. Chemicals effects also vary between body tissues. For example, some environmental toxins affect specific organs like the liver or the brain.
A major reason for these differences is that species, individuals, and organs all have different kinds and amounts of enzymes. Enzymes are part of the machinery of living cells that allow cells to react to drugs and to break down chemicals. In humans, a large group of enzymes in the liver are responsible for the majority of drug interactions and side effects. Different levels of these enzymes are responsible for many of the variations in the effects of chemicals.
There is a need for a technology to rapidly, effectively, and economically test the health effects of chemicals. Such chemicals include potential new life-saving pharmaceuticals, environmental contaminants, workplace toxins, potential carcinogens, and beneficial food chemicals, among many others. Current methods either involve testing on live animals, which can be time-consuming and costly, or involve testing in the laboratory, which is often not relevant to human health.
At the same time, there is a need for a technology to speed up the drug development process. One major bottleneck in the race to develop new life-saving treatments is the optimization of new drug candidates. When a potential new drug is discovered, teams of chemists often modify its chemical structure to create new compounds, and then screen them for improved efficacy and reduced side effects. This process currently is extremely expensive, intricate, time-consuming, and labor intensive, and generates significant amounts of chemical waste. These drawbacks can severely limit the number of optimizations that can be tried, so the final drug resulting from the process may not be the best drug that is possible.
There is therefore a need across many different disciplines for a technology to rapidly, effectively, and economically test the health effects of chemicals. In particular, there is a need for a technology to test chemicals, especially pharmaceuticals, on human metabolic enzymes. Furthermore, there is a need to optimize new drug candidates rapidly and economically.